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Blood, 1 July 2005, Vol. 106, No. 1, pp. 193-200. Prepublished online as a Blood First Edition Paper on March 3, 2005; DOI 10.1182/blood-2004-12-4886. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4886v1 106/1/193    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Terra, R. Articles by Perreault, C. Search for Related Content PubMed PubMed Citation Articles by Terra, R. Articles by Perreault, C. Related Collections Signal Transduction Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY T-cell generation by lymph node resident progenitor cells Rafik Terra, Isabelle Louis, Richard Le Blanc, Sophie Ouellet, Juan Carlos Zúñiga-Pflücker, and Claude Perreault From the Institute of Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada; Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada; Centre Hospitalier Universitaire de Sherbrooke, Fleurimont, QC, Canada; and Department of Immunology, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, ON, Canada. In the thymus, 2 types of Lin–Sca-1+ (lineage-negative stem cell antigen-1–positive) progenitors can generate T-lineage cells: c-Kithi interleukin-7 receptor –negative (c-KithiIL-7R–) and c-KitloIL-7R+. While c-KithiIL-7R– progenitors are absent, c-KitloIL-7R+ progenitors are abundant in the lymph nodes (LNs). c-KitloIL-7R+ progenitors undergo abortive T-cell commitment in the LNs and become arrested in the G1 phase of the cell cycle because they fail both to up-regulate c-myb, c-myc, and cyclin D2 and to repress junB, p16INK4a, and p21Cip1/WAF. As a result, development of LN c-KitloIL-7R+ progenitors is blocked at an intermediate CD44+CD25lo development stage in vivo, and LN-derived progenitors fail to generate mature T cells when cultured with OP9-DL1 stromal cells. LN stroma can provide key signals for T-cell development including IL-7, Kit ligand, and Delta-like–1 but lacks Wnt4 and Wnt7b transcripts. LN c-KitloIL-7R+ progenitors are able to generate mature T cells when cultured with stromal cells producing wingless-related MMTV integration site 4 (Wnt4) or upon in vivo exposure to oncostatin M whose signaling pathway intersects with Wnt. Thus, supplying Wnt signals to c-KitloIL-7R+ progenitors may be sufficient to transform the LN into a primary T-lymphoid organ. These data provide unique insights into the essence of a primary T-lymphoid organ and into how a cryptic extrathymic T-cell development pathway can be amplified. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. L. Veinotte, T. Y. F. Halim, and F. Takei Unique subset of natural killer cells develops from progenitors in lymph node Blood, April 15, 2008; 111(8): 4201 - 4208. [Abstract] [Full Text] [PDF] R. Terra, H. Luo, X. Qiao, and J. Wu Tissue-specific expression of B-cell translocation gene 2 (BTG2) and its function in T-cell immune responses in a transgenic mouse model Int. Immunol., March 1, 2008; 20(3): 317 - 326. [Abstract] [Full Text] [PDF] M.-E. Blais, S. Brochu, M. Giroux, M.-P. Belanger, G. Dulude, R.-P. Sekaly, and C. Perreault Why T Cells of Thymic Versus Extrathymic Origin Are Functionally Different J. Immunol., February 15, 2008; 180(4): 2299 - 2312. [Abstract] [Full Text] [PDF] Q.-L. Hao, A. A. George, J. Zhu, L. Barsky, E. Zielinska, X. Wang, M. Price, S. Ge, and G. M. Crooks Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7- lympho-myeloid thymic progenitors Blood, February 1, 2008; 111(3): 1318 - 1326. [Abstract] [Full Text] [PDF] L. M. Stephenson, B. Sammut, D. B. Graham, J. Chan-Wang, K. L. Brim, A. S. Huett, A. V. Miletic, T. Kloeppel, A. Landry, R. Xavier, et al. DLGH1 Is a Negative Regulator of T-Lymphocyte Proliferation Mol. Cell. Biol., November 1, 2007; 27(21): 7574 - 7581. [Abstract] [Full Text] [PDF] M. Giroux, E. Yurchenko, J. St.-Pierre, C. A. Piccirillo, and C. Perreault T Regulatory Cells Control Numbers of NK Cells and CD8{alpha}+ Immature Dendritic Cells in the Lymph Node Paracortex J. Immunol., October 1, 2007; 179(7): 4492 - 4502. [Abstract] [Full Text] [PDF] C. Baron, M.-C. Meunier, E. Caron, C. Cote, M. J. Cameron, D. J. Kelvin, R. LeBlanc, V. Rineau, and C. Perreault Asynchronous Differentiation of CD8 T Cells That Recognize Dominant and Cryptic Antigens J. Immunol., December 15, 2006; 177(12): 8466 - 8475. [Abstract] [Full Text] [PDF] I. Maillard, B. A. Schwarz, A. Sambandam, T. Fang, O. Shestova, L. Xu, A. Bhandoola, and W. S. Pear Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation Blood, May 1, 2006; 107(9): 3511 - 3519. [Abstract] [Full Text] [PDF]

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